The role of resources in achieving target competitive positions

Competitive positioning has become an essential component of modern marketing management. For a firm to target effective positions for its products and services, it needs to decide on the market segment (where it will compete) as well as the differential advantage it will emphasise (how it will compete). Until recently, empirical research on positioning has received little attention, while substantial insight has been gained with respect to the concept of competitive positioning. Furthermore, Hooley, Moller and Broderick have highlighted the lack of empirical studies relative to theoretical ones related to positioning in general and to the relationship between positioning and the different components of each competitive positioning that a firm might choose. This study focuses on product competitive positioning in over-the-counter (OTC) pharmaceuticals in the British market. It was found that certain resources underpin specific competitive positions.

Attentional shifts towards an expected visual target alter the level of alpha-band oscillatory activity in the human calcarine cortex

Neuronal operations associated with the top-down control process of shifting attention from one locus to another involve a network of cortical regions, and their influence is deemed fundamental to visual perception. However, the extent and nature of these operations within primary visual areas are unknown. In this paper, we used magnetoencephalography (MEG) in combination with magnetic resonance imaging (MRI) to determine whether, prior to the onset of a visual stimulus, neuronal activity within early visual cortex is affected by covert attentional shifts. Time/frequency analyses were used to identify the nature of this activity. Our results show that shifting attention towards an expected visual target results in a late-onset (600 ms postcue onset) depression of alpha activity which persists until the appearance of the target. Independent component analysis (ICA) and dipolar source modeling confirmed that the neuronal changes we observed originated from within the calcarine cortex. Our results further show that the amplitude changes in alpha activity were induced not evoked (i.e., not phase-locked to the cued attentional task). We argue that the decrease in alpha prior to the onset of the target may serve to prime the early visual cortex for incoming sensory information. We conclude that attentional shifts affect activity within the human calcarine cortex by altering the amplitude of spontaneous alpha rhythms and that subsequent modulation of visual input with attentional engagement follows as a consequence of these localized changes in oscillatory activity. © 2005 Elsevier B.V. All rights reserved.

The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin-deficient tumors

Merlin has broad tumor-suppressor functions as its mutations have been identified in multiple benign tumors and malignant cancers. In all schwannomas, the majority of meningiomas and 1/3 of ependymomas Merlin loss is causative. In neurofibromatosis type 2, a dominantly inherited tumor disease because of the loss of Merlin, patients suffer from multiple nervous system tumors and die on average around age 40. Chemotherapy is not effective and tumor localization and multiplicity make surgery and radiosurgery challenging and morbidity is often considerable. Thus, a new therapeutic approach is needed for these tumors. Using a primary human in vitro model for Merlin-deficient tumors, we report that the Ras/Raf/mitogen-activated protein, extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) scaffold, kinase suppressor of Ras 1 (KSR1), has a vital role in promoting schwannomas development. We show that KSR1 overexpression is involved in many pathological phenotypes caused by Merlin loss, namely multipolar morphology, enhanced cell-matrix adhesion, focal adhesion and, most importantly, increased proliferation and survival. Our data demonstrate that KSR1 has a wider role than MEK1/2 in the development of schwannomas because adhesion is more dependent on KSR1 than MEK1/2. Immunoprecipitation analysis reveals that KSR1 is a novel binding partner of Merlin, which suppresses KSR1's function by inhibiting the binding between KSR1 and c-Raf. Our proteomic analysis also demonstrates that KSR1 interacts with several Merlin downstream effectors, including E3 ubiquitin ligase CRL4DCAF1. Further functional studies suggests that KSR1 and DCAF1 may co-operate to regulate schwannomas formation. Taken together, these findings suggest that KSR1 serves as a potential therapeutic target for Merlin-deficient tumors.

Bacterial resistance to antibiotics:modified target sites

Alteration in the target sites of antibiotics is a common mechanism of resistance. Examples of clinical strains showing resistance can be found for every class of antibiotic, regardless of the mechanism of action. Target site changes often result from spontaneous mutation of a bacterial gene on the chromosome and selection in the presence of the antibiotic. Examples include mutations in RNA polymerase and DNA gyrase, resulting in resistance to the rifamycins and quinolones, respectively. In other cases, acquisition of resistance may involve transfer of resistance genes from other organisms by some form of genetic exchange (conjugation, transduction, or transformation). Examples of these mechanisms include acquisition of the mecA genes encoding methicillin resistance in Staphylococcus aureus and the various van genes in enterococci encoding resistance to glycopeptides. © 2005 Elsevier B.V. All rights reserved.

In silico identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination

Adjuvants are substances that enhance immune responses and thus improve the efficacy of vaccination. Few adjuvants are available for use in humans, and the one that is most commonly used (alum) often induces suboptimal immunity for protection against many pathogens. There is thus an obvious need to develop new and improved adjuvants. We have therefore taken an approach to adjuvant discovery that uses in silico modeling and structure-based drug-design. As proof-of-principle we chose to target the interaction of the chemokines CCL22 and CCL17 with their receptor CCR4. CCR4 was posited as an adjuvant target based on its expression on CD4(+)CD25(+) regulatory T cells (Tregs), which negatively regulate immune responses induced by dendritic cells (DC), whereas CCL17 and CCL22 are chemotactic agents produced by DC, which are crucial in promoting contact between DC and CCR4(+) T cells. Molecules identified by virtual screening and molecular docking as CCR4 antagonists were able to block CCL22- and CCL17-mediated recruitment of human Tregs and Th2 cells. Furthermore, CCR4 antagonists enhanced DC-mediated human CD4(+) T cell proliferation in an in vitro immune response model and amplified cellular and humoral immune responses in vivo in experimental models when injected in combination with either Modified Vaccinia Ankara expressing Ag85A from Mycobacterium tuberculosis (MVA85A) or recombinant hepatitis B virus surface antigen (rHBsAg) vaccines. The significant adjuvant activity observed provides good evidence supporting our hypothesis that CCR4 is a viable target for rational adjuvant design.

Mind-Reading Accuracy in Intimate Relationships:Assessing the Roles of the Relationship, the Target, and the Judge

Using a video-review procedure, multiple perceivers carried out mind-reading tasks of multiple targets at different levels of acquaintanceship (50 dating couples, friends of the dating partners, and strangers). As predicted, the authors found that mind-reading accuracy was (a) higher as a function of increased acquaintanceship, (b) relatively unaffected by target effects, (c) influenced by individual differences in perceivers' ability, and (d) higher for female than male perceivers. In addition, superior mind-reading accuracy (for dating couples and friends) was related to higher relationship satisfaction, closeness, and more prior disclosure about the problems discussed, but only under moderating conditions related to sex and relationship length. The authors conclude that the nature of the relationship between the perceiver and the target occupies a pivotal role in determining mind-reading accuracy.

Electronics:a case study of economic value added in target costing

Whilst target costing and strategic management accounting (SMA) continue to be of considerable interest to academic accountants, both suffer from a relative dearth of empirically based research. Simultaneously, the subject of economic value added (EVA) has also been the subject of little research at the level of the individual firm.The aim of this paper is to contribute to both the management accounting and value based management literatures by analysing how one major European based MNC introduced EVA into its target costing system. The case raises important questions about both the feasibility of cascading EVA down to product level and the compatibility of customer facing versus shareholder focused systems of performance management. We provide preliminary evidence that target costing can be used to align both of these perspectives, and when combined with other SMA techniques it can serve as " the bridge connecting strategy formulation with strategy execution and profit generation" ( Ansari et al., 2007, p. 512). © 2012 Elsevier Ltd.

Effect of target distance on accommodative amplitude measured using the minus lens technique

Background: The aim was to investigate the effect on the measured amplitude of accommodation and repeatability of using the minus lens technique with the target at distance or near. Methods: Forty-three students (average age: 21.17 ± 1.50 years, 35 female) had their amplitude of accommodation measured with minus lenses on top of their distance correction in a trial frame with the target at far (6.0m) or near (0.4m). The minus lens power was gradually added with steps of 0.25D. Measurements were taken on two occasions at each distance, which were separated by a time interval of at least 24 hours. Results: The measured amplitude at six metres was significantly lower than that with the target at 40cm, by 1.56 ± 1.17D (p < 0.001) and this varied between individuals (r = 0.716, intraclass correlation coefficient = 0.439). With either target distance, repeated measurement was highly correlated (r > 0.9) but the agreement was better at 6.0m (±0.74D) than at 40cm (± 0.92D). Conclusion: The measurements of the amplitude of accommodation with the minus lens technique using targets at far or near are not comparable and the difference between the target distances may provide clinically relevant information. © 2013 Optometrists Association Australia.

Tissue Transglutaminase (TG2) is a potential therapeutic target in the treatment of chemoresistant breast cancer

Tissue transglutaminase (TG2) has been suggested to be a key player in the progression and metastasis of chemoresistant breast cancer. One of the foremost survival signalling pathways implicated in causing drug resistance in breast cancer is the constitutive activation of NFκB (Nuclear Factor -kappa B) induced by TG2. This study provides a mechanism by which TG2 constitutively activates NFκB which in turn confers chemoresistance to breast cancer cells against doxorubicin. Breast cancer cell lines with varying expression levels of TG2 as well as TG2 null breast cancer cells transfected with TG2 were used as the major cell models for this study. This study made use of cell permeable and impermeable TG2 inhibitors, specific TG2 and Rel A/ p65 targeting siRNA, TG2 functional blocking antibodies, IKK inhibitors and a specific targeting peptide against Rel A/p65 to investigate the pathway of activation involved in the constitutive activation of NFκB by TG2 leading to drug resistance. Crucial to the activation of Rel A/p65 and drug resistance in the breast cancer cells is the interaction between the complex of IκBα and Rel A/p65 with TG2 which results in the dimerization of Rel A/p65 and polymerization of IκBα. The association of TG2 with the IκBα-NFκB complex was determined to be independent of IKKα/β function. The polymerized IκBα is degraded in the cytoplasm by the μ-calpain pathway which allows the cross linked Rel A/ p65 dimers to translocate into the nucleus. Using R283 and ZDON (cell permeable TG2 activity inhibitors) and specific TG2 targeting siRNA, the Rel A/ p65 dimer formation could be inhibited. Co-immunoprecipitation studies confirmed that the phosphorylation of the Rel A/p65 dimers at the Ser536 residue by IKKε took place in the cell nucleus. Importantly, this study also investigated the transcriptional regulation of the TGM2 gene by the pSer536 Rel A/ p65 dimer and the importance of this TG2-NFκB feedback loop in conferring drug resistance to breast cancer cells. This data provides evidence that TG2 could be a key therapeutic target in the treatment of chemoresistant breast cancer.

Target spatial frequency determines the response to conflicting defocus- and convergence-driven accommodative stimuli

Asthenopia, or visual fatigue, is a frequent complaint from observers of stereoscopic three-dimensional displays. It has been proposed that asthenopia is a consequence of anomalous oculomotor responses generated by conflict between accommodative and convergence stimuli. The hypothesis was examined by measuring accommodation and convergence continuously with a Shin-Nippon SRW5000 infrared autorefractor and a limbus tracking device. Subjects viewed a high contrast Maltese Cross target at three levels of Gaussian filter target blur under conditions of relatively low- and high-conflict between accommodation and convergence stimuli, the latter inducing the sensation of stereopsis. Under the low-conflict conditions accommodation was stable, but convergence-driven accommodation was dominant when the target was extremely blurred. Under the high-conflict conditions the role of convergence-driven accommodation increased systematically with the degree of target blur. It is proposed that defocus-driven accommodation becomes weak when the target comprises low spatial frequency components. Large accommodative overshoots to step stimuli that are not blurred or only mildly blurred were consistently observed and are attributed to the initial accommodative response being convergence-driven. Whereas the possibility that high-conflict conditions are a cause of asthenopia has been previously reported, this is the first evidence that they specifically affect accommodative responses while viewing stereoscopic displays. © 2005 Elsevier Ltd. All rights reserved.

Cortical dynamics and synchronization related to multiple target consolidation under rapid-serial-visual-presentation conditions

The present report reviews behavioural, electroencephalographic, and especially magnetoencephalographic findings on the cortical mechanisms underlying attentional processes that separate targets from distractors and that ensure durable target representations for goal-directed action. A common way of investigation is to observe the system’s overt and covert behaviour when capacity limitations are reached. Here we focus on the aspect of temporally enhanced processing load, namely on performance deficits occurring under rapid-serial-visual-presentation (RSVP) conditions. The most prominent of these deficits is the so-called “attentional blink” (AB) effect. We first report MEG findings with respect to the time course of activation that shows modulations around 300 ms after target onset which reflect demands and success of target consolidation. Then, findings regarding long-range inter-area phase synchronization are reported that are hypothesized to mediate communication within the attentional network. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioural performance. Furthermore, enhanced vigilance of the system elicits systematically increased synchronization indices. A hypothetical framework is sketched out that aims at explaining limitations in multiple target consolidation under RSVP conditions.

A modified semi-oriented radial measure for target setting with negative data

Over the last few years Data Envelopment Analysis (DEA) has been gaining increasing popularity as a tool for measuring efficiency and productivity of Decision Making Units (DMUs). Conventional DEA models assume non-negative inputs and outputs. However, in many real applications, some inputs and/or outputs can take negative values. Recently, Emrouznejad et al. [6] introduced a Semi-Oriented Radial Measure (SORM) for modelling DEA with negative data. This paper points out some issues in target setting with SORM models and introduces a modified SORM approach. An empirical study in bank sector demonstrates the applicability of the proposed model. © 2014 Elsevier Ltd. All rights reserved.