A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries

Combinatorial chemistry has become an invaluable tool in medicinal chemistry for the identification of new drug leads. For example, libraries of predetermined sequences and head-to-tail cyclized peptides are routinely synthesized in our laboratory using the IRORI approach. Such libraries are used as molecular toolkits that enable the development of pharmacophores that define activity and specificity at receptor targets. These libraries can be quite large and difficult to handle, due to physical and chemical constraints imposed by their size. Therefore, smaller sub-libraries are often targeted for synthesis. The number of coupling reactions required can be greatly reduced if the peptides having common amino acids are grouped into the same sub-library (batching). This paper describes a schedule optimizer to minimize the number of coupling reactions by rotating and aligning sequences while simultaneously batching. The gradient descent method thereby reduces the number of coupling reactions required for synthesizing cyclic peptide libraries. We show that the algorithm results in a 75% reduction in the number of coupling reactions for a typical cyclic peptide library.

Adolescents' reactions to universal and indicated prevention programs for depression: Perceived stigma and consumer satisfaction

There is a common view that one of the major considerations in selecting between universal and indicated interventions is the marked stigma produced by the latter. However, to date there has been no empirical examination of this assumption. The current study examined reported stigma and program satisfaction following two school-based interventions aimed at preventing depression in 532 middle adolescents. The interventions were conducted either across entire classes by classroom teachers (universal delivery) or in small high risk groups by mental health professionals (indicated delivery). The indicated delivery was associated with significantly greater levels of perceived stigma, but effect sizes were small and neither program was associated with marked stigma in absolute terms. Perceived stigma was more strongly associated with aspects of the individual including being male and showing greater externalizing symptomatology. In contrast, the indicated program was evaluated more positively by both participants and program leaders and effect sizes for these measures of satisfaction were moderate to large. The results point to the need for further empirical evaluation of both perceived stigma and program satisfaction in providing balanced considerations of the value of indicated and universal programs.

Cognitive asymmetry in employee emotional reactions to leadership behaviors

This article is predicated on the idea that leaders shape workplace affective events. Based on Affective Events Theory (AET), I argue that leaders are sources of employee positive and negative emotions at work. Certain leader behaviors displayed during interactions with their employees are the sources of these affective events. The second theoretical underpinning of the article is the Asymmetry Effect of emotion. Consistent with this theory, employees are more likely to recall negative incidents than positive incidents. In a qualitative study, evidence that these processes exist in the workplace was found. Leader behaviors were sources of positive or negative emotional responses in employees; employees recalled more negative incidents than positive incidents, and they recalled them more intensely and in more detail than positive incidents. Consequently, leaders may need to exercise their emotional intelligence to generate emotional uplifts to overcome the hassles in the workplace that employees seem to remember so vividly. (c) 2006 Elsevier Inc. All rights reserved.

Direct access to functionalized cyclic enones using Mannich, Morita-Baylis-Hillman and elimination reactions

A series of highly functionalized cyclic enones were obtained from Mannich, Morita-Baylis-Hiliman and elimination reaction with cyclic enones.

Introduction of routine outcome measures: staff reactions and issues for consideration

The aim of this study was to explore clinician reactions to (i) the introduction of routine outcome measures and (ii) the utility of outcomes data in clinical practice. Focus group discussions (n = 34) were conducted with mental health staff (n = 324) at approximately 8 months post implementation of routine outcome measures. A semi-structured interview schedule was used to collect data on two key issues; reactions to the introduction of outcome measures and factors influencing the utility of outcomes data in clinical practice. Data from the discussion groups were analysed using content analysis to isolate emerging themes. While the majority of participants endorsed the collection and utilization of outcomes data, many raised questions about the merits of the initiative. Ambivalence, competing work demands, lack of support from senior medical staff, questionable evidence to support the use of outcome measures, and fear of how outcomes data might be used emerged as key issues. At 8 months post implementation a significant number of clinical staff remained ambivalent about the benefits of outcome measurement and had not engaged in the process. The shift to a service model driven by outcomes and case-mix data will take time and resources to achieve. Implications for nursing staff are discussed.

Reactions to positive deviance: Social identity and attribution dimensions

This research examines whether evaluations of positive deviates (i.e. high achieving group members) are influenced by the attributions they make for their performance. We argue that ingroup positive deviates who make group attributions help enhance the ingroup's image and thus attract favorable evaluations. In Experiment 1, ingroup positive deviates who made group attributions were generally evaluated more favorably than ingroup positive deviates who made individual attributions. There was also evidence that the positive deviates' attribution style influenced group and self-evaluations. Evaluations of outgroup positive deviates were not influenced by their attribution style. In Experiment 2, an ingroup positive deviate who was successful and attributed that success to the group was upgraded relative to an ingroup positive deviate who made individual attributions. Group evaluations were also higher when the positive deviate made group attributions. This pattern did not emerge when the positive deviate failed. The results are discussed from a social identity perspective.

A calreticulin-like protein from endoparasitoid venom fluid is involved in host hemocyte inactivation

During oviposition, most endoparasitoid wasps inject maternal factors into their hosts to interfere with host immune reactions and ensure successful development of their progeny. Since encapsulation is a major cellular defensive response of insects against intruding parasites, parasitoids have developed numerous mechanisms to suppress the host encapsulation capability by interfering with every step in the process, including recognition, adherence and spreading. In previous studies, components of Cotesia rubecula venom were shown to inhibit melanization of host hemolymph by interfering with the prophenoloxidase activation cascade and facilitate expression of polydnavirus genes. Here we report the isolation and characterization of another venom protein with similarity to calreticulin. Results indicate that C rubecula calreticulin (CrCRT) inhibits hemocyte spreading behavior, thus preventing encapsulation of the developing parasitoid. It is possible that the protein might function as an antagonist competing for binding sites with the host hemocyte calreticulin, which mediates early-encapsulation reactions. (c) 2005 Elsevier Ltd. All rights reserved.

Comparative studies of hyperhomodesmotic reactions for the calculation of standard heats of formation of fullerenes

How can the accuracy of the calculated standard heats of formation Delta H-f(0) of fullerenes be improved? How reliable are the values of Delta H-f(0) calculated from hyperhomodesmotic reactions? This work is the first to address these questions. By comparing the results obtained from three hyperhomodesmotic reactions containing only fullerenes, it is illustrated that both the resonance contribution and the strain energy contribution should be considered in the construction of hyperhomodesmotic reactions. An attempt to construct such hyperhomodesmotic reactions for fullerenes has been carried out, and several new insights are indicated.

Using fear appeals to promote cancer screening - are we scaring the wrong people?

There is debate regarding the use of fear appeals (emphasizing severe threats to health) in social marketing, to encourage preventive behaviours, such as screening for breast cancer. While it has been found that fear appeals may result in attitude and behaviour change there is also the risk of inciting inappropriate levels of fear, motivating the wrong audience or instigating maladaptive behaviour in the target group such as denial or defensive avoidance. This study examined the impact of an experimental threat manipulation for mammography screening on a group of women in regional Australia. The study found that varying the level of threat had no impact on stated intentions of the women to undergo mammographic screening. However, it also found that high-threat messages resulted in stronger negative emotional reactions and greater perceived susceptibility among younger women who are not the target group for screening in Australia. The results of this study emphasize the importance of limiting the use of high levels of threat in social marketing campaigns, and ensuring that campaigns are appropriately designed to specifically impact upon and motivate the target group. Copyright © 2006 John Wiley & Sons, Ltd.

Quadriceps activity and movement reactions in response to unpredictable sagittal support-surface translations in women with patellofemoral pain

Patellofemoral pain (PFP) may be related to unfavorable knee joint loading. Delayed and/or reduced activity of vastus medialis obliquus (VMO) and different movement patterns have been identified in individuals with PFP in some studies, whereas other studies have failed to show a difference compared to non-affected controls. The discrepancy between study results may depend on the different tasks that have been investigated. No previous study has investigated these variables in postural responses to unpredictable perturbations in PFP. Whole body three dimensional kinematics and surface EMG of quadriceps muscles activation was studied in postural responses to unpredictable support surface translations in 17 women with PFP who were pain free at the time of testing, and 17 matched healthy controls. The results of the present study showed earlier onset of VMO activity and associated changes in kinematics to anterior platform translation in the PFP subjects. We suggest that the relative timing between the portions quadriceps muscles may be task specific and part of an adapted response in attempt to reduce knee joint loading. This learned response appears to remain even when the pain is no longer present.

The moderating effects of goal orientations on reactions to goal-performance discrepancies

Due to the growing popularity of goal setting programs within organisations, an understanding of the mechanisms underlying the dynamic regulation of performance is paramount (Williams, Donovan, & Dodge, 2000). Goals serve as standards or referents by which behaviour is directed and evaluated. Whilst their importance is well established in the existing literature (e.g. Locke & Latham, 1990), more recent research has highlighted the potential importance of goal-performance discrepancies. Moreover, the relationship between goal-performance discrepancies and outcomes such as self-efficacy and personal goals appears to vary between people (Schmidt & Chambers, 2002). Of interest in the current study was how these relationships were impacted by goal orientation. Ninety-seven participants completed 30 two-minute trials of an Air Traffic Control task. Task specific goal orientation was measured prior to commencement of the task and measures of self-efficacy and personal task goals were taken at each trial to assess the within-person relationships between goal performance discrepancies and each of these dependant variables, as well as the moderating effects of goal orientations on these relationships. Analysis supported the existence of a positive relationship between goal-performance discrepancies and outcome variables, with performance-approach and –avoidance orientations significantly moderating these associations. Implications and future directions are discussed.