A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response. © 2012 Elsevier B.V. All rights reserved.

Polymer-peptide conjugate hydrogels:towards controlled drug delivery

Peptide-based materials exhibit remarkable supramolecular self-assembling behavior, owing to their overwhelming propensity to from hierarchical structures from a-helices and ß-sheets. Coupling a peptide sequence to a synthetic polymer chain allows greater control over the final physical properties of the supermolecular material. So-called ‘polymer-peptide conjugates’ can be used to create biocompatible hydrogels which are held together by reversible physical interactions. Potentially, the hydrogels can be loaded with aqueous-based drug molecules, which can be injected into targeted sites in the body if they can exhibit a gel-sol-gel transition under application and removal of a shear force. In this review, we introduce this topic to readers new to the field of polymer-peptide conjugates, discussing common synthetic strategies and their self-assembling behavior. The lack of examples of actual drug delivery applications from polymer-peptide conjugates is highlighted in an attempt to incite progress in this area.

The role of the sales employee in securing customer satisfaction

Purpose: Previous research has emphasized the pivotal role that salespeople play in customer satisfaction. In this regard, the relationship between salespeople's attitudes, skills, and characteristics, and customer satisfaction remains an area of interest. The paper aims to make three contributions: first, it seeks to examine the impact of salespeople's satisfaction, adaptive selling, and dominance on customer satisfaction. Second, this research aims to use dyadic data, which is a better test of the relationships between constructs since it avoids common method variance. Finally, in contrast to previous research, it aims to test all of the customers of salespeople rather than customers selected by salespeople. Design/methodology/approach: The study employs multilevel analysis to examine the relationship between salespeople's satisfaction with the firm on customer satisfaction, using a dyadic, matched business-to-business sample of a large European financial service provider that comprises 188 customers and 18 employees. Findings: The paper finds that customers' evaluation of service quality, product quality, and value influence customer satisfaction. The analysis at the selling firm's employee level shows that adaptive selling and employee satisfaction positively impact customer satisfaction, while dominance is negatively related to customer satisfaction. Practical implications: Research shows that customer-focus is a key driver in the success of service companies. Customer satisfaction is regarded as a prerequisite for establishing long-term, profitable relations between company and customer, and customer contact employees are key to nurturing this relationship. The role of salespeople's attitudes, skills, and characteristics in the customer satisfaction process are highlighted in this paper. Originality/value: The use of dyadic, multilevel studies to assess the nature of the relationship between employees and customers is, to date, surprisingly limited. The paper examines the link between employee attitudes, skills, and characteristics, and customer satisfaction in a business-to-business setting in the financial service sector, differentiating between customer- and employee-level drivers of business customer satisfaction.

Global marketing of industrial products:are interpersonal relationships always critical?

The present paper examines the issue of whether interpersonal relationships are critical for global marketing of industrial products. The fields of relationship marketing, IMP group research, sales research, and network theory have stressed the importance of interpersonal relationships in the business-to-business or industrial marketing context. In contrast to this emphasis on interpersonal relationships, we argue that industrial firms can both conceive and enhance marketing strategies based on developing high quality and consistent processes, products, services or outcomes (consistent processes and outcomes). Such strategies are especially important given the fact that developing interpersonal relationships is expensive due to their reliance on frequent and/or face-to-face communications. In this paper, we examine industry and country contexts that lead to the choice of alternative industrial product marketing strategies and highlight some future research directions and managerial implications.

Personal selling of high-technology products:the solutions-selling imperative

Traditional focus on the study of high-technology firms and products has practically ignored the importance and potential contributions of the sales force, especially in business-to-business marketing. This article suggests that traditional sales force strategies associated with high-technology products have been supply driven (i.e., driven by the strategies of the marketing firm). We suggest that in order to enhance the success of high-technology products and services, firms need to be more demand driven in their sales structures (i.e., driven by the strategies of the buying firm). We suggest that it is imperative that high-technology firms adopt “solution selling” to enhance high-technology adoption as well as enhance competitiveness. We describe this change in focus and draw out its various managerial and academic implications.

The variance in sales performance explained by the knowledge structures of salespeople

The last major study of sales performance variance explained by salespeople attributes was by Churchill et al. (1985). They examined the effect of role, skills, motivation, personal factors, aptitude, and organizational/environmental factors on sales performance—factors that have dominated the sales performance area. About the same time, Weitz, Sujan, and Sujan (1986) introduced the concepts of salespeople's knowledge structures. Considerable work on the relationship of the elements of knowledge structures and performance can be found in the literature. In this research note, we determine the degree to which sales performance can be explained by knowledge structure variables, a heretofore unexplored area. If knowledge structure variables explain more variance than traditional variables, then this paper would be a call to further research in this area. In examining this research question in a retail context, we find that knowledge structure variables explain 50.2 percent of the variance in sales performance. We also find that variance explained by knowledge structures is significantly different based on gender. The impact of knowledge structures on performance was higher for men than for women. The models using education demonstrated smaller differences.

The impact of transactional and relational strategies in business markets:an agenda for inquiry

The impetus for the special issue of Industrial Marketing Management is the importance of understanding the implications of transactional and relational strategies in business-to-business contexts. The objective of the special issue is to integrate conceptual and empirical research in this area. We highlight research that extends current thinking in the area to ensure that this special issue serves an impetus for future research on this important topic.

Investigating polymer-peptide conjugates and electrospinning for the production of advanced materials

This thesis describes the production of advanced materials comprising a wide array of polymer-based building blocks. These materials include bio-hybrid polymer-peptide conjugates, based on phenylalanine and poly(ethylene oxide), and polymers with intrinsic microporosity (PIMs). Polymer-peptides conjugates were previously synthesised using click chemistry. Due to the inherent disadvantages of the reported synthesis, a new, simpler, inexpensive protocol was sought. Three synthetic methods based on amidation chemistry were investigated for both oligopeptide and polymerpeptide coupling. The resulting conjugates produced were then assessed by various analytical techniques, and the new synthesis was compared with the established protocol. An investigation was also carried out focussing on polymer-peptide coupling via ester chemistry, involving deprotection of the carboxyl terminus of the peptide. Polymer-peptide conjugates were also assessed for their propensity to self-assemble into thixotropic gels in an array of solvent mixtures. Determination of the rules governing this particular self-assembly (gelation) was required. Initial work suggested that at least four phenylalanine peptide units were necessary for self-assembly, due to favourable hydrogen bond interactions. Quantitative analysis was carried out using three analytical techniques (namely rheology, FTIR, and confocal microscopy) to probe the microstructure of the material and provided further information on the conditions for self-assembly. Several polymers were electrospun in order to produce nanofibres. These included novel materials such as PIMs and the aforementioned bio-hybrid conjugates. An investigation of the parameters governing successful fibre production was carried out for PIMs, polymer-peptide conjugates, and for nanoparticle cages coupled to a polymer scaffold. SEM analysis was carried out on all material produced during these electrospinning experiments.

Facile synthesis of poly(3-hexylthiophene)-block-poly(ethylene oxide) copolymers via Steglich esterification

Poly(ethylene oxide) has been coupled to poly(3-hexylthiophene) using esterification to produce pure diblock copolymers, highly relevant for use in organic electronic devices. The new synthetic route described herein uses a metal-free coupling step, for the first time, to afford well-defined polymers in high yields following facile purification.

Identification and evaluation of agents isolated from traditionally used herbs against Ophiophagus hannah venom

The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydroandrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future.

Facile synthesis of polymer-peptide conjugates via direct amino acid coupling chemistry

Polymer-peptide conjugates (also known as biohy-brids) are attracting considerable attention as injectable materials owing to the self-assembling behavior of the peptide and the ability to control the material properties using the polymer component. To this end, a simple method for preparing poly(ethylene oxide)-oligophenylalanine polymer-peptide conjugates (mPEOm-F n-OEt) using isobutylchloroformate as the activating reagent has been identified and developed. The synthetic approach reported employs an industrially viable route to produce conjugates with high yield and purity. Moreover, the approach allows judicious selection of the precursor building blocks to produce libraries of polymer-peptide conjugates with complete control over the molecular composition. Control over the molecular make-up of the conjugates allows fine control of the physicochemical properties, which will be exploited in future studies into the prominent self-assembling behavior of such materials. © 2013 Wiley Periodicals, Inc.

Non-stationary stochastic inventory lot-sizing with emission and service level constraints in a carbon cap-and-trade system

Firms worldwide are taking major initiatives to reduce the carbon footprint of their supply chains in response to the growing governmental and consumer pressures. In real life, these supply chains face stochastic and non-stationary demand but most of the studies on inventory lot-sizing problem with emission concerns consider deterministic demand. In this paper, we study the inventory lot-sizing problem under non-stationary stochastic demand condition with emission and cycle service level constraints considering carbon cap-and-trade regulatory mechanism. Using a mixed integer linear programming model, this paper aims to investigate the effects of emission parameters, product- and system-related features on the supply chain performance through extensive computational experiments to cover general type business settings and not a specific scenario. Results show that cycle service level and demand coefficient of variation have significant impacts on total cost and emission irrespective of level of demand variability while the impact of product's demand pattern is significant only at lower level of demand variability. Finally, results also show that increasing value of carbon price reduces total cost, total emission and total inventory and the scope of emission reduction by increasing carbon price is greater at higher levels of cycle service level and demand coefficient of variation. The analysis of results helps supply chain managers to take right decision in different demand and service level situations.

Bagging model with cost sensitive analysis on diabetes data

Diabetes patients might suffer from an unhealthy life, long-term treatment and chronic complicated diseases. The decreasing hospitalization rate is a crucial problem for health care centers. This study combines the bagging method with base classifier decision tree and costs-sensitive analysis for diabetes patients' classification purpose. Real patients' data collected from a regional hospital in Thailand were analyzed. The relevance factors were selected and used to construct base classifier decision tree models to classify diabetes and non-diabetes patients. The bagging method was then applied to improve accuracy. Finally, asymmetric classification cost matrices were used to give more alternative models for diabetes data analysis.

Returns on key accounts:do the results justify the expenditures?

Purpose – The use of key accounts has become a mature trend and most industrial firms use this concept in some form. Selling firms establish key account teams to attend to important customers and consolidate their selling activities. Yet, despite such increased efforts on behalf of key accounts, sufficient research has not quantified the returns on key account strategy nor has it firmly established performance differences between key and non-key accounts within a firm. In response to this shortcoming, this study aims to examine returns on key accounts. Design Methodology/approach – Data were collected from a global consulting firm. The data collection started two years after the implementation of the key account program. Data were collected on recently acquired customers (within the previous year) at two time periods: year 1 and year 3 (based on company access of data). Findings – Initially, key accounts perform as well or better than other types of accounts. However, in the long term, key accounts are less satisfied, less profitable and less beneficial for a firm’s growth than other types of accounts. Because the returns to key account expenditures, thus, appear mixed, firms should be cautious in expanding their key account strategies. Research limitations implications – The study contributes to research in three areas. First, most research on the effectiveness of key accounts refers to the between-firm level, whereas this study examines the effect within a single firm. Second, this study examines the temporal aspects of key accounts, namely, what happens to key accounts over time, in comparison with other accounts in a fairly large sample. Third, it considers the survival rates of key accounts versus other types of accounts. Practical implications – The authors suggest that firms also need to track their key accounts better because the results show that key accounts are less satisfied, less profitable and less beneficial for a firm’s growth than other types of accounts. Originality/value – Extant research has not examined these issues.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.