Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin, Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from freeDNAwere present in positive ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA, highlighting the need for obtaining ESI mass spectra of non-covalent complexes under a range of experimental conditions. Negative ion spectra of mixtures of the minor groove binder Hoechst 33258 with DNA containing a known minor groove binding sequence were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting an alternative binding mode was possible either in solution or in the gas phase. When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1 complexes were formed, consistent with existence of binding modes other than minor groove binding. The data presented suggest that comparison of positive and negative ion ESI-MS spectra might provide an insight into various binding modes in both solution and the gas phase.

Entrepreneurship in a developing economy : preliminary findings

Theories of entrepreneurship have largely been informed by research in western contexts, and recent calls for research attention to entrepreneurship in developing countries highlight the need for accurate information about entrepreneurship in this field. In addition, some findings from such research have highlighted the critical research needs in this area (Bruton, Ahlstrom & Obloj, 2009). This paper reports early findings from one study of a longitudinal research program with entrepreneurs in an Eastern African context, in a society largely affected by colonization and a long-standing civil war. Entrepreneurs in this study are recipients of micro-credit loans as well as elementary business training. Findings from a review of microloans indicate that entrepreneurial activities are largely in the form of local entrepreneurship rather than systemic entrepreneurship (Suatet, 2011) and the benefits of business improvements achieved from micro-loans are enhanced by feelings of agency and purpose regarding future business activities. Implications for theory and practice are presented.

Stakeholders' perceptions of data utility in the context of ERP outcomes

A substantial body of literature exists identifying factors contributing to under-performing Enterprise Resource Planning systems (ERPs), including poor communication, lack of executive support and user dissatisfaction (Calisir et al., 2009). Of particular interest is Momoh et al.’s (2010) recent review identifying poor data quality (DQ) as one of nine critical factors associated with ERP failure. DQ is central to ERP operating processes, ERP facilitated decision-making and inter-organizational cooperation (Batini et al., 2009). Crucial in ERP contexts is that the integrated, automated, process driven nature of ERP data flows can amplify DQ issues, compounding minor errors as they flow through the system (Haug et al., 2009; Xu et al., 2002). However, the growing appreciation of the importance of DQ in determining ERP success lacks research addressing the relationship between stakeholders’ requirements and perceptions of ERP DQ, perceived data utility and the impact of users’ treatment of data on ERP outcomes.

UV Photodissociation Action Spectroscopy of Haloanilinium Ions in a Linear Quadrupole Ion Trap Mass Spectrometer

UV-vis photodissociation action spectroscopy is becoming increasingly prevalent because of advances in, and commercial availability of, ion trapping technologies and tunable laser sources. This study outlines in detail an instrumental arrangement, combining a commercial ion-trap mass spectrometer and tunable nanosecond pulsed laser source, for performing fully automated photodissociation action spectroscopy on gas-phase ions. The components of the instrumentation are outlined, including the optical and electronic interfacing, in addition to the control software for automating the experiment and performing online analysis of the spectra. To demonstrate the utility of this ensemble, the photodissociation action spectra of 4-chloroanilinium, 4-bromoanilinium, and 4-iodoanilinium cations are presented and discussed. Multiple photoproducts are detected in each case and the photoproduct yields are followed as a function of laser wavelength. It is shown that the wavelength-dependent partitioning of the halide loss, H loss, and NH3 loss channels can be broadly rationalized in terms of the relative carbon-halide bond dissociation energies and processes of energy redistribution. The photodissociation action spectrum of (phenyl)Ag-2 (+) is compared with a literature spectrum as a further benchmark.

Paint spray mass spectrometry for the detection of additives from polymers on conducting surfaces

Paint Spray is developed as a direct sampling ionisation method for mass spectrometric analysis of additives in polymer-based surface coatings. The technique simply involves applying an external high voltage (5 kV) to the wetted sample placed in front of the mass spectrometer inlet and represents a much simpler ionisation technique compared to those currently available. The capabilities of Paint Spray are demonstrated herein with the detection of four commercially available hindered amine light stabilisers; TINUVIN® 770, TINUVIN® 292, TINUVIN® 123 and TINUVIN® 152 directly from thermoset polyester-based coil coatings. Paint Spray requires no sample preparation or pre-treatment and combined with its simplicity - requiring no specialised equipment - makes it ideal for use by non-specialists. The application of Paint Spray for industrial use has significant potential as sample collection from a coil coating production line and Paint Spray ionisation could enable fast quality control screening at high sensitivity.

Time to face the fats : What can mass spectrometry reveal about the structure of lipids and their interactions with proteins?

Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.

Imaging of human lens lipids by desorption electrospray ionization mass spectrometry

The lipid composition of the human lens is distinct from most other tissues in that it is high in dihydrosphingomyelin and the most abundant glycerophospholipids in the lens are unusual 1-O-alkyl-ether linked phosphatidylethanolamines and phosphatidylserines. In this study, desorption electrospray ionization (DESI) mass spectrometry-imaging was used to determine the distribution of these lipids in the human lens along with other lipids including, ceramides, ceramide-1-phosphates, and lyso 1-O-alkyl ethers. To achieve this, 25 μm lens slices were mounted onto glass slides and analyzed using a linear ion-trap mass spectrometer equipped with a custom-built, 2-D automated DESI source. In contrast to other tissues that have been previously analyzed by DESI, the presence of a strong acid in the spray solvent was required to desorb lipids directly from lens tissue. Distinctive distributions were observed for [M + H]+ ions arising from each lipid class. Of particular interest were ionized 1-O-alkyl phosphatidylethanolamines and phosphatidylserines, PE (18:1e/18:1), and PS (18:1e/18:1), which were found in a thin ring in the outermost region of the lens. This distribution was confirmed by quantitative analysis of lenses that were sectioned into four distinct regions (outer, barrier, inner, and core), extracted and analyzed by electrospray ionization tandem mass spectrometry. DESI-imaging also revealed a complementary distribution for the structurally-related lyso 1-O-alkyl phosphatidylethanolamine, LPE (18:1e), which was localized closer to the centre of the lens. The data obtained in this study indicate that DESI-imaging is a powerful tool for determining the spatial distribution of human lens lipids. © 2010 American Society for Mass Spectrometry.

Multi-modal object tracking using dynamic performance metrics

Intelligent surveillance systems typically use a single visual spectrum modality for their input. These systems work well in controlled conditions, but often fail when lighting is poor, or environmental effects such as shadows, dust or smoke are present. Thermal spectrum imagery is not as susceptible to environmental effects, however thermal imaging sensors are more sensitive to noise and they are only gray scale, making distinguishing between objects difficult. Several approaches to combining the visual and thermal modalities have been proposed, however they are limited by assuming that both modalities are perfuming equally well. When one modality fails, existing approaches are unable to detect the drop in performance and disregard the under performing modality. In this paper, a novel middle fusion approach for combining visual and thermal spectrum images for object tracking is proposed. Motion and object detection is performed on each modality and the object detection results for each modality are fused base on the current performance of each modality. Modality performance is determined by comparing the number of objects tracked by the system with the number detected by each mode, with a small allowance made for objects entering and exiting the scene. The tracking performance of the proposed fusion scheme is compared with performance of the visual and thermal modes individually, and a baseline middle fusion scheme. Improvement in tracking performance using the proposed fusion approach is demonstrated. The proposed approach is also shown to be able to detect the failure of an individual modality and disregard its results, ensuring performance is not degraded in such situations.

Mothers' sleep and driving in the postpartum period

Introduction: Previous studies investigating mothers’ sleep in the postpartum period commonly demonstrated elevated levels of sleepiness in this population. A Karolinska Sleepiness Scale (KSS) rating of 5 or above is associated with an exponential increase in vehicle crash risk. To date, no studies have investigated the relationship between mothers’ sleep in the postpartum period and their driving behaviour. Methods: Sleep-wake diary data was collected from 14 mother-infant dyads during two 7-day assessment periods when the infants were 6 and 12 weeks old. The mothers’ indicated all driving episodes during these weeks and their respective sleepiness level using the KSS. Semi-structured interviews were conducted with the mothers when their infant was 12 weeks old. Results: The infants slept significantly more than their mothers at 6 weeks and 12 weeks of age. During both time points, mothers and infants had a similar number of night awakenings (waking between 22:00 and 06:00), with some mothers experiencing greater than 19 awakenings over 7 nights. Notably, 36% of the mothers did not experience a continuous sleep period longer than 4.5 hours when their infant was 6 weeks old. A total of 141 driving episodes were reported during the 7 day assessment period when the infants were 6 weeks old. Over 50% of the driving episodes were denoted with a KSS score of 5 or above. Strategies mothers cited they employed during this period included only driving when feeling alert, postponing driving until another person is present, and driving in the morning when less sleepy. Conclusion: Mothers are experiencing disrupted sleep at night and some mothers do not obtain more than 4.5 hours of continuous sleep during the early postpartum weeks. In this sample, some mothers reported self-regulating driving behaviour, however over half of the driving episodes were undertaken with a sleepiness rating linked with elevated crash risk.

Built to last versus meant to end : time bounds specification in strategic alliances

This article explores an important temporal aspect of the design of strategic alliances by focusing on the issue of time bounds specification. Time bounds specification refers to a choice on behalf of prospective alliance partners at the time of alliance formation to either pre-specify the duration of an alliance to a specific time window, or to keep the alliance open-ended (Reuer & Ariňo, 2007). For instance, Das (2006) mentions the example of the alliance between Telemundo Network and Mexican Argos Comunicacion (MAC). Announced in October 2000, this alliance entailed a joint production of 1200 hours of comedy, news, drama, reality and novella programs (Das, 2006). Conditioned on the projected date of completing the 1200 hours of programs, Telemundo Network and MAC pre-specified the time bounds of the alliance ex ante. Such time-bound alliances are said to be particularly prevalent in project-based industries, like movie production, construction, telecommunications and pharmaceuticals (Schwab & Miner, 2008). In many other instances, however, firms may choose to keep their alliances open-ended, not specifying a specific time bound at the time of alliance formation. The choice between designing open-ended alliances that are “built to last”, versus time bound alliances that are “meant to end” is important. Seminal works like Axelrod (1984), Heide & Miner (1992), and Parkhe (1993) demonstrated that the choice to place temporal bounds on a collaborative venture has important implications. More specifically, collaborations that have explicit, short term time bounds (i.e. what is termed a shorter “shadow of the future”) are more likely to experience opportunism (Axelrod, 1984), are more likely to focus on the immediate present (Bakker, Boros, Kenis & Oerlemans, 2012), and are less likely to develop trust (Parkhe, 1993) than alliances for which time bounds are kept indeterminate. These factors, in turn, have been shown to have important implications for the performance of alliances (e.g. Kale, Singh & Perlmutter, 2000). Thus, there seems to be a strong incentive for organizations to form open-ended strategic alliances. And yet, Reuer & Ariňo (2007), one of few empirical studies that details the prevalence of time-bound and open-ended strategic alliances, found that about half (47%) of the alliances in their sample were time bound, the other half were open-ended. What conditions, then, determine this choice?

Strategic renewal and competitive advantage in opportunity-driven and conservative new ventures

Strategic renewal has received relatively little attention in the context of new ventures. We examine the relationship among strategic renewal, competitive advantage and performance in opportunity-driven and conservative new ventures. Based on longitudinal data of a random sample of almost 373 new ventures, the link between strategic renewal and performance can be better understood by adding the mediating role of competitive advantage. Our results indicate that increased levels of strategic renewal positively relate to competitive advantage in conservative ventures, but not in opportunity-driven ventures. These findings place a different perspective on the dominant view that entrepreneurs should be opportunity maximizers. It suggests that both conservative and opportunity-driven new ventures can be successful if they follow different paths of strategic renewal in shaping competitive advantage.

HRM in professional service firms : engendering commitment to what or whom?

Professional service firms (PSFs) present HR professionals with a number of unique challenges, as they share characteristics of both service and knowledge intensive organizations. While many of these firms are relying on High Commitment Work Practices (HCWPs) to enhance critical employee behaviors such as service quality and turnover, the analysis presented in this paper raises questions about traditional understandings of commitment in professional service environments. In particular, data from three Danish financial investment PSFs suggest that employees are more committed to developing and promoting their own professions than to the organization itself, which has important implications for the way in which HCWPs are designed and utilized. In addition, the focus of HCWP research has favored the use of social exchange theory as an underpinning framework for considering the impact of HR practices on employee commitment. In the context of PSFs, we question the applicability of social exchange theory and instead draw upon the Ability-Motivation-Opportunity (AMO) framework (1982) to analyze how specific HRM practices contribute to the development of commitment, and to successful organizational outcomes in PSFs.

The applicability of aesthetic knowledge in organizational decision making processes

We argue that aesthetic knowledge, which is a form of tacit knowledge of beauty and related concepts, is an important, yet under-researched, topic in the study of organizational decision making processes. The significance of aesthetic knowledge for decision making processes is derived from its universal application by humans to commonplace practices; its use as the basis of decision criteria in complex situations to which the effective application of logic and reason is difficult; and its role both in assisting cognition in general and in enabling the choice of solutions generated from rational decision making processes. Despite its importance, the empirical research examining the application of aesthetic knowledge in organizational decision making processes is limited. Further detailed study of aesthetic knowledge in the context of organizational decision making processes is required to extend the recent movement in the field aimed at examining the role that extrarational, human-centered factors play in organizational decisions.