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Summary Ants (Hymenoptera: Formicidae) are familiar inhabitants of most terrestrial environments. Although we are aware of the ability of many species to sting, knowledge of ant venom chemistry remains limited. Herein, we describe the discovery and characterization of an O-linked glycopeptide (Mg7a) as a major component of the venom of the ant Myrmecia gulosa. Electron transfer dissociation and higher-energy collisional dissociation tandem mass spectrometry were used to localize three α-N-acetylgalactosaminyl residues (α-GalNAc) present on the 63-residue peptide. To allow for functional studies, we synthesized the full-length glycosylated peptide via solid-phase peptide synthesis, combined with diselenide–selenoester ligation-deselenization chemistry. We show that Mg7a is paralytic and lethal to insects, and triggers pain behavior and inflammation in mammals, which it achieves through a membrane-targeting mode of action. Deglycosylation of Mg7a renders it insoluble in aqueous solution, suggesting a key solubilizing role of the O-glycans., Graphical abstract, Highlights • The 63-amino acid glycopeptide Mg7a is a major component of Myrmecia gulosa venom • Mg7a is insecticidal and causes pain behavior and inflammation in mice • Mg7a targets cell membranes causing a leak in ion conductance • Glycosylation is important for Mg7a solubility, Natural product chemistry; Biomolecules; Neuroscience

The present work focuses on the remediation of Methylene Blue dye (MB) by adsorption on Fuller's earth clay (FE). The optimum batch limits for MB adsorption are; pH 8; equilibration time 3 ​h; initial concentration 100 ​mg ​L−1; agitation speed 300 ​rpm; a dose of adsorbent 2 ​g ​L−1, and temperature 25 ​°C. FE clay was characterized using XRD and FESEM. XRD analysis indicated montmorillonite to be the major component of FE. FESEM images indicated clay surface to be layered with high surface area and porosity thereby making it an excellent material for dye adsorption. Classical Langmuir, Modified Langmuir, Freundlich, and BET adsorption isotherms were studied to investigate the adsorption mechanism of MB on FE. Modified Langmuir isotherm fits well for adsorption of MB on FE with an adsorption capacity of 11587 ​mg ​g−1. Kinetic studies revealed the adsorption process to follow Pseudo Second-order kinetics with the energy of activation 28 ​kJ/mol, indicating the adsorption process to be physisorption. Thermodynamic studies indicated the adsorption process to be spontaneous and endothermic. The Artificial Neural Network (ANN) model was employed in the FE system, and the model confirmed its applicability. According to error analysis, ANN was found to be more appropriate model than pseudo second-order model. Sensitivity calculations from ANN data indicated the pH of adsorption to be the most influential factor in MB adsorption with 29% relative importance. The sorption process may be practically valuable on an industrial scale to remediate MB from water assets at an economical price.

Introduction: We conducted a randomized, observer-blind, non-inferiority, parallel-group clinical study of diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b conjugate (pentavalent) vaccination of infants in India. Goals were to determine whether the seropositivity rate after vaccination via disposable-syringe jet injector (DSJI) was non-inferior to that via needle and syringe (N-S), and to compare the safety of vaccination by the two methods. Methods: Healthy children received a three-dose series of vaccine intramuscularly by DSJI or N-S beginning at 6–8 weeks of age. Immunoglobulin G antibody levels were measured by ELISA at 4–6 weeks after the third dose. The main secondary endpoint was safety, measured as injection site and systemic reactions. Discussion: The study was stopped early out of caution beyond that specified in the protocol stopping criteria, after the Data Safety Committee noted a higher frequency of injection site reactions, especially moderate and severe, in the DSJI group. As a result, 128 subjects—DSJI group 61; N-S group 67—completed the study, rather than the 340 planned, and the study was not sufficiently powered to compare immunogenicity endpoints for the groups. Descriptive statistics indicate that seropositivity induced by vaccination with the DSJI was similar to that of N-S for all five antigens. Pentavalent vaccine includes whole-cell pertussis vaccine and an aluminum adjuvant, which may have contributed to the higher number of local reactions with the DSJI. The reactions caused no serious or long-term sequelae, and may be more acceptable in other populations or circumstances.US National Institutes of Health clinical trials identifier: NCT02409095. Keywords: DTP-HB-Hib vaccine, Jet injector, DSJI, Vaccine adjuvant, Immunogenicity, Injection site reactions

The complement system is a key player in innate immunity and a major effector arm of humoral immunity. Its activating components are a group of plasma proteins, whose triggering consists of a series of sequential protease-based steps similar to the coagulation, fibrinolytic, and contact pathways. Complement activation is linked to cellular responses by the recognition of cleaved complement protein fragments by receptors on leukocytes and vascular cells. The three primary roles of complement in host defense against infection are to (1) activate an inflammatory response; (2) opsonize microbial pathogens for immune adherence; and (3) damage membranes, including lysis of susceptible organisms. The complement cascade is amplified at several steps so that it has the potential to induce a rapid and massive opsonic and inflammatory response. Complement activation is normally highly targeted and strictly regulated to focus this response. However, complement activation also contributes to tissue injury in infectious, autoimmune, and acute and chronic inflammatory diseases. This chapter gives an overview of the “workings” of the complement system, a brief review of complement deficiency, and discussion of the role of complement in diseases of inflammation, autoimmunity, and debris disposal.

This chapter includes introduction of plastics and their recycling techniques. Polymers can be divided into two main groups: thermoplastic and thermosetting. Properties of plastics such as durability, chemical, and mechanical stability make it difficult to reuse. To avoid undesired accumulation of plastic waste, recycling is the best option to opt for. Polyethylene terephthalate and polyurethane foams are being used for a lot of applications, thus their recycling is a major concern for most of the developing countries.

Rheology is the study of how materials deform and flow as a result of an external force, and is one tool that is used by formulators to help characterize semisolid dosage forms. The two extremes of rheological behavior are elastic and viscous (or plastic) behavior. Between elastic and viscous behavior lies the real world of most substances, which are viscoelastic materials. In the case of viscoelastic materials, timescales are important to rheological behavior—when deformation is fast, materials exhibit solid-like behavior; when deformation is slow, materials exhibit fluid-like behavior. The rheology of semisolid formulations provides critical information for product and process performance, including product stability. Rheology-based measurements can help predict which formulations might exhibit flocculation, coagulation, or coalescence, resulting in undesired effects such as settling, creaming, or separation. Viscosity is a measure of the resistance of a material to flow, and is just one aspect of the rheological profile of a formulation.

Different semisolid dosage forms and various excipients used in pharmaceutical formulations are discussed. The current approach of the US Food Drug Administration for the classification of semisolid dosages is presented. The formation and formulation of emulsions are discussed in detail. The formulation of liposomes, one of the major drug-delivery systems used in pharmaceutical dosages, is also discussed.

Current trends are to use newer, targeted drug-delivery approaches to effectively deliver smaller dosages to target sites—thereby reducing toxicity and possible unwanted side effects. Different drug-delivery systems including emulsions, liposomes, and nanodrug delivery systems are reviewed and discussed. Methods of producing liposomes, and some existing drug products based on liposomes, are presented.

Both optical and electron microscopy techniques are discussed in relation to pharmaceutical formulation development. Microscopy is a very useful tool in pharmaceutical research, formulation development, process development, and quality control of manufactured products. Microscopy is routinely used for the examination of the drug material (the API—Active Pharmaceutical Ingredient), excipients (inactive ingredients present in the finished dosages), or the drug product. Both particle size and morphology are key characteristics for product performance; morphology is particularly important for aerosol dosage forms, in which particle flow is critical. Microscopes that use illumination sources in the ultraviolet the infrared regions are also available, and their application in pharmaceutical product development is gaining popularity. The importance of electron microscopes (both scanning and transmission) is discussed and the application of atomic force microscopy in pharmaceutical research has been pointed out.

Nanotechnology offers promising solutions for improving nutrition, health and wellbeing by delivering nutrients through a variety of food vehicles with different physicochemical properties including consistency and texture. This review focuses on the digestive, absorptive and postabsorptive fate of nanoparticles (NPs). Nutrients that have received attention include vitamins A, D, E, C, β-carotene, iron and to some extent zinc and calcium. There is tremendous scope for nanotechnological applications to other nutrients eg, amino acids, folic acid, B12, and so on. However, concerted efforts should address the pros and cons of ingesting NPs vis-a-vis chronic exposure and residence time in human body. Studies of storage/shelf life, biocompatibility, bioavailability and risk assessment of different type of nanomaterials are required to gauge safety when different NPs are incorporated in varied food vehicles. Regulations to protect consumers need to be brought in place before commercial applications of NPs.

Many types of aerosol products exist—such as deodorants, antiperspirants, hair sprays, insecticides, oils, polishes, and paints. The pressurized metered-dose inhaler is one type of aerosol product that is used to deliver drugs as a mist or spray via the pulmonary system. The common formulation types used for aerosol and nasal spray products are solutions, suspensions, and emulsions. This chapter looks at the manufacturing processes for aerosol and nasal spray products, the types of excipients that are used in aerosol and nasal spray formulations, and the effect that the excipients can have on the physical characteristics of the expelled product.

Polymers are extremely versatile ingredients in semisolid formulations, being used to create a range of different effects, from thickening to preservation and conditioning. Polymers are macromolecules consisting of a long-chain backbone of smaller repeating units (monomers) and side groups. Polymers that contain only a single type of repeat unit are known as homopolymers, whereas polymers containing a mixture of repeat units are known as copolymers. Depending on the type of polymer, the backbone can be either linear or branched. The side groups influence the functional properties of the polymer, such as how well it thickens, conditions, and forms films.

This chapter covers test methods typically used to evaluate and characterize semisolid formulations. The methods have been subdivided into physical, chemical, and microbiological, as well as separating them into tests that might typically be performed on all semisolid formulations, and those that are specific to a type of product. When they are performed during the product lifetime, and what information they can provide, is also described.

This chapter provides an overview of surfactants and surface properties that play important roles in pharmaceutical formulations. Examples of ionic, nonionic, and zwitterionic surfactants are provided. Structures of different lipids and their applications as excipients or actives are discussed. A brief introduction to the HLB system is provided. Examples of drug products in the marketplace that use various surfactants and lipids are listed indicating the importance of surfactants and lipids in pharmaceutical formulations. Surface and interfacial tension measurement, and the significance of the role of surface tension and contact angle in designing the pharmaceutical formulations has been discussed.

Although the regulatory landscape for pharmaceutical semisolid products is well established, the regulations are under constant review to improve the quality, safety, and efficacy of products both under development and in the marketplace. This chapter highlights some of the development/quality guidance in place at the time of writing and, more importantly, provides references to where the most up-to-date compliance information can be obtained.

Liquid and semisolid formulations contain many different functional ingredients depending on their physical form and intended use—for example, pH buffers, antioxidants, microbial preservatives, chelators, osmolality agents, penetration enhancers, thickeners, emulsifiers, solvent systems, humectants, pharmaceutically active ingredients, moisturizers, fragrances, flavorings, and colorants. When and how these ingredients are added to the formulation will determine whether the finished formulation is successful—aesthetically, functionally, and stable. This chapter looks at how formulations are typically put together, gives examples of different mixing systems, shows how Quality by Design can be applied to formulation development, and how to evaluate the stability of a formulation.

Trikatu churna is one of the commonly used Ayurvedic formulations in the traditional system of medicine in India for the treatment of agnimandya, i.e. anorexia. Trikatu contains equal amounts of finely powdered rhizomes of Zingiber officinale Roscoe (Zingiberaceae) and fruits of Piper longum L. and Piper nigrum L. (Piperaceae). The chief objective of the study was to determine the antianorectic effects of three drugs individually and to compare these effects with the effect of Trikatu. The activity of the drugs was studied after anorexia was induced in rats by (1) physical stress arising from immobilization for 60 min; (2) intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS, 100 μg/kg body weight); and (3) intraperitoneal administration of fluoxetine (8 mg/kg body weight). Similar doses of the extracts were tested on freely feeding rats and on rats that had been deprived of food for 20 h. Corticotrophin-releasing factor (CRF, 0.3 μg/rat) can induce anxiogenic-like behavior and reduced food intake. This model was also studied, and the results were compared. The components of Trikatu churna failed to individually reverse the inhibition of feeding. In contrast, Trikatu churna pretreatment reversed stress-, fluoxetine- and CRF-induced anorexia. The study provides strong evidence of the synergistic action of Ayurvedic formulas and also proves the ability of Trikatu churna to reduce stress and CRF-induced anorexia.

The study sought to build on earlier work by identifying factors associated with the frequency of natural disasters and the resulting mortality. Countries prone to natural disasters in the decade 1970–1979 continued to be so in the next two decades. Geophysical factors (e.g., whether landlocked, size of country) had an important role in explaining inter-country variations in the occurrence of natural disasters. Deaths varied with the number of disasters; they also varied with (lagged) deaths in the previous decade; poor countries suffered more deaths; and, controlling for these and other effects, larger countries suffered more deaths. The payoff from learning from experience is high; even moderate learning can save a large number of lives. Growth acceleration helps avert deaths through more resources for disaster prevention and mitigation capabilities. A challenge for development assistance is to combine growth acceleration with speedy relief and a durable reduction in vulnerability to natural disasters.

A major goal for understanding the role of thyroid hormone (TH) in development has been to identify genes regulated by TH in different tissues during frog metamorphosis. The exquisite dependence of metamorphosis on TH also provides a model to study TH endocrine disruption. To identify such TH-regulated genes and select biomarkers for TH endocrine disruption, global gene expression analyses in tadpoles using microarrays have been done in 21 studies, involving five frog species, seven organs, and four endocrine disrupting chemicals. As expected, each organ has a unique set of genes associated with its tissue-specific metamorphic outcome, and functions ascribed to many of these genes correspond to histological changes induced by TH. Also, the large number of transcription factors identified in microarrays is consistent with the molecular mechanisms of TH action. On the other hand, microarray analysis has also revealed interesting findings not predicted from previous morphological or molecular studies. Furthermore, endocrine disruption studies identified candidate biomarkers for TH disruption, and the mechanisms of action of several endocrine disrupting chemicals have been examined. The microarray studies described here have produced a wealth of data on gene expression that requires further functional studies to elucidate the roles of these genes in development and endocrine disruption.

To study tropospheric ozone variability over the Iberian Peninsula (IP), NASA Langley TOR data have been analyzed for the 1979–2005 period. The maximum tropospheric ozone concentration over the entire IP was found in June (∼41 DU) and a minimum in December (∼29 DU). However the maximum tropospheric ozone concentration was found over West Atlantic Coast (WAC) (∼44 DU), followed by Mediterranean Coast (MC) (∼42 DU), North Atlantic Coast (NAC) (∼41 DU), Central Iberian Peninsula (CIP) (∼40 DU) and Pyrenees Mountain Range (PMR) (∼39 DU) during June-July. The high concentration of tropospheric ozone in July over the Atlantic Ocean near IP is due to the presence of Azores anticyclone and related photochemistry and dynamics, and affects the observed higher tropospheric ozone concentration over WAC zone. Strong seasonal cycle in tropospheric ozone concentration has been observed with large variation over NAC (∼49%), followed by WAC (∼48%) and MC (∼41%) compared to CIP and PMR (∼38%) zones. When the data are compared over the IP for the two periods (1979–1993 and 1997–2005), a systematic increase in the number of months with higher tropospheric ozone concentration has been observed during the second period with respect to the first. These increases are almost 8% to 24% over NAC, 6% to 17% over WAC, 5% to 24% over CIP, 6% to 23% over MC and 13% to 18% over PMR, zones. It has been observed that topography, climatology and population density distribution plays a crucial role in the variability of tropospheric ozone concentration over the IP.

Publisher Summary Polymer chain structure is characterized by a hierarchical model based on statistical scaling transitions in a polymer coil at thermal equilibrium. On the smallest scale short-range enthalpic interactions dominate and the chain displays local persistence associated with the Kuhn length. At larger sizes, the structure depends on a balance among thermal energy, chain entropy, and long-range interaction enthalpy. The large-scale structure is based on the Brownian model with perturbations associated with concentration, temperature, externally applied force, and structural topology related to chain branching. These factors can lead to changes in the chain scaling. A linear coil displays four possible large-scale states, extended chain in response to an external field, self-avoiding walk, Gaussian, and collapsed states. The coil can respond to perturbations through the formation of a size of scaling transition, which is called a blob. Depending on the perturbation, the nature of the scaling transition varies. These include concentration blob, thermal blob, and tensile blob. Other scaling transitions are likely to exist in response to structural perturbations.

This paper proposes an approach using quality loss functions and multicriteria optimization procedure to determine appropriate process parameter values for producing quality products in a continuous casting system. Quality of a continuously cast product depends on the process conditions during the casting process. From the information available in the literature and industry, 17 critical quality conditions have been identified which have to be satisfied to prevent defect formation during casting. Each of these process conditions are connected to one or more than one process parameters and the process parameter values are to be selected such that all these 17 quality conditions are satisfied simultaneously. The optimization procedure suggested in the present study involves representing the relationship between the responses and the process variables in the form of an objective function and finding the best set of values for the process variables. The objective function is formulated as a loss function, which establishes a functional relationship between the input variables or process parameters and the quality criteria. The optimum values of the process parameters were obtained by minimizing the loss function using simulated annealing optimization algorithm. The details are presented in this paper with the help of a specific case., © Elsevier

A group of stable ruthenium(II) and (III) mixed-ligand tris-chelated complexes of the type [Run+(bpy)(L)2]z+ (1–8, n=2, Z=0; 9, n=3, Z=1) have been synthesized and characterized (bpy=2,2′-bipyridine; L=anionic form of the ligands, ROC(S)SK, (R=Me, Et, n Pr, i Pr, n Bu, i Bu, –CH2–Ph) or (EtO)2P(S)SNH4 or (Et)2NC(S)SNa). The complexes 1–8 are diamagnetic and electrically neutral and the complex 9 is one-electron paramagnetic and behaves as 1:1 electrolyte in acetonitrile solvent. The complexes 1–8 and 9 display two MLCT transitions near 530, 370 nm and 663, 438 nm respectively. Intra-ligand bipyridine based π–π* transition is observed near 300 nm. The complexes 1–8 exhibit room-temperature emission from the highest energy MLCT band (~370 nm). At room temperature the lifetime of the excited states for the complexes 2 and 8 are found to be 90 and 95 ns respectively. In acetonitrile solution the complexes 1–9 show a reversible ruthenium(III)–ruthenium(II) couple in the range −0.08 → 0.40 V and irreversible ruthenium(III)–ruthenium(IV) oxidation in the range 1.19–1.45 V vs Ag/AgCl. One reversible bipyridine reduction is observed for each complex in the range −1.70 → −1.85 V vs Ag/AgCl. The presence of trivalent ruthenium in the oxidized solution for one complex 1 is evidenced by the axial EPR spectrum at 77 K. The isolated trivalent complex 9 also exhibits an axial EPR spectrum at 77 K. The EPR spectra of the trivalent ruthenium complexes (1+ and 9) have been analyzed to furnish values of distortion parameters (Δ(cm−1)→1+, 3689; 9, 3699) and energies of the two expected ligand field transitions (ν1(cm−1)→1+, 3489; 9, 3497 and ν2(cm−1)→1+, 4339; 9, 4348) within the t2 shell. One of the ligand field transitions has been experimentally observed at 4673 cm−1 for complex 9 and which close to the computed ν2 value (4348 cm−1)., © Elsevier

A comprehensive model is developed for interfacial polymerization (IP), which provides new insights into the kinetics of film formation, the molecular weight distribution of the polymer as well as the mechanism of polymer precipitation. We incorporate a more general reaction scheme as well as polymer phase separation both by nucleation of the polymer-rich phase as well as by spinodal decomposition. The model predictions are verified against experimental data for unstirred Nylon 6–10 system. The model predicts that spinodal decomposition is the dominant mechanism of polymer phase separation at short reaction times. Film growth by nucleation of the polymer-rich phase dominates at larger times. The model also predicts the dominance of the nucleation mode of film growth with dilution of the organic phase. This model provides a further step towards a rational design and prediction of properties of membranes/capsules produced by interfacial polymerization., © Elsevier

Arachidonic acid (AA) decreases coronary arterial resistance in the isolated perfused rabbit heart and relaxes bovine and human coronary artery strips. PGE 2 or PGF 2α contracts these coronary strips and does not affect coronary arterial resistance in the isolated rabbit heart. This suggested that a different arachidonate metabolite may be responsible for these responses. The endogenous phospholipids of the isolated rabbit heart and the coronary artery strips were labelled with [ 14 C ] AA. The primary metabolite of AA released by the heart and the coronary strips was a novel prostaglandin, and some PGE 2 ; no free PGH 2 could be demonstrated. The novel PG was resistant to base hydrolysis and sodium borohydoride reduction. The mobility of this metabolite in multiple chromatography systems was similar to that of 6-keto-PGF 1α . This metabolite demonstrated essentially no biologic activity. The precursor of 6-keto-PGF 1α , PGH 2 , relaxes bovine coronary artery strips, but the endoperoxide itself is rapidly degraded. A potent coronary relaxant is produced by incubating PGH 2 with microsomes from bovine coronary arteries and is present in the cardiac venous effluent following hormone or AA stimulation. The coronary relaxant degraded to the stable end-product 6-keto-PGF 1α . The biologically active component of this novel pathway of arachidonate metabolism appears to be an intermediate (PGX) between PGH 2 and the final 6-keto-PGF 1α -like-product. This intermediate proves to be a potent coronary vasodilator and a probable endogenous determinant of local vascular tone.