Rh-bound trimethylenemethane variants generated from the interaction of a Rh-carbenoid with an allene have been applied to the synthesis of substituted 3,4-fused pyrroles. The pyrrole products are ...useful starting points for the syntheses of various dipyrromethene ligands. Furthermore, the methodology has been applied to a synthesis of the natural product cycloprodigiosin, which demonstrates antitumor and immunosuppressor activity.
Purpose
– The purpose of this paper is to review, critique and develop a research agenda for the Elaboration Likelihood Model (ELM). The model was introduced by Petty and Cacioppo over three decades ...ago and has been modified, revised and extended. Given modern communication contexts, it is appropriate to question the model’s validity and relevance.
Design/methodology/approach
– The authors develop a conceptual approach, based on a fully comprehensive and extensive review and critique of ELM and its development since its inception.
Findings
– This paper focuses on major issues concerning the ELM. These include model assumptions and its descriptive nature; continuum questions, multi-channel processing and mediating variables before turning to the need to replicate the ELM and to offer recommendations for its future development.
Research limitations/implications
– This paper offers a series of questions in terms of research implications. These include whether ELM could or should be replicated, its extension, a greater conceptualization of argument quality, an explanation of movement along the continuum and between central and peripheral routes to persuasion, or to use new methodologies and technologies to help better understanding consume thinking and behaviour? All these relate to the current need to explore the relevance of ELM in a more modern context.
Practical implications
– It is time to question the validity and relevance of the ELM. The diversity of on- and off-line media options and the variants of consumer choice raise significant issues.
Originality/value
– While the ELM model continues to be widely cited and taught as one of the major cornerstones of persuasion, questions are raised concerning its relevance and validity in 21st century communication contexts.
The efficient and selective synthesis of functionalized seven‐membered rings remains an important pursuit within synthetic organic chemistry, as this motif appears in numerous drug‐like molecules and ...natural products. Use of cycloaddition reactions remains an attractive approach for their construction within the perspective of atom and step economy. Additionally, the ability to combine multiple components in a single reaction has the potential to allow for efficient combinatorial strategies of diversity‐oriented synthesis. The inherent entropic penalty associated with achieving these transformations has impressively been overcome with development of catalysis, whereby the reaction components can be pre‐organized through activation by transition‐metal‐catalysis. The fine‐tuning of metal/ligand combinations as well as reaction conditions allows for achieving chemo‐, regio‐, diastereo‐ and enantioselectivity in these transformations. Herein, we discuss recent advances in transition‐metal‐catalyzed construction of seven‐membered rings via combination of 2–4 components mediated by a variety of metals. An emphasis is placed on the mechanistic aspects of these transformations to both illustrate the state of the science and to highlight the unique application of novel processes of transition‐metals in these transformations.
The seven‐membered ring systems constitute a vital structural motif in a great number of biologically active natural products. The transition‐metal‐catalyzed cycloaddition reaction has unimpeachably emerged as a powerful and straightforward tool to render shorter synthetic routes for complex molecules. This Review summarizes recent progresses in this field.
To determine if using a combination of hospital administrative data and ambulatory care physician billings can accurately identify patients with congestive heart failure (CHF), we tested 9 algorithms ...for identifying individuals with CHF from administrative data.
The validation cohort against which the 9 algorithms were tested combined data from a random sample of adult patients from EMRALD, an electronic medical record database of primary care physicians in Ontario, Canada, and data collected in 2004/05 from a random sample of primary care patients for a study of hypertension. Algorithms were evaluated on sensitivity, specificity, positive predictive value, area under the curve on the ROC graph and the combination of likelihood ratio positive and negative.
We found that that one hospital record or one physician billing followed by a second record from either source within one year had the best result, with a sensitivity of 84.8% and a specificity of 97.0%.
Population prevalence of CHF can be accurately measured using combined administrative data from hospitalization and ambulatory care.
The nine membrane-delimited eukaryotic adenylyl cyclases are pseudoheterodimers with an identical domain order of seven (nine) distinct subdomains. Bioinformatics show that the protein evolved from a ...monomeric bacterial progenitor by gene duplication and fusion probably in a primordial eukaryotic cell around 1.5 billion years ago. Over a timespan of about 1 billion years, the first fusion product diverged into nine highly distinct pseudoheterodimeric isoforms. The evolutionary diversification ended approximately 0.5 billion years ago because the present isoforms are found in the living fossil coelacanth, a fish. Except for the two catalytic domains, C1 and C2, the mAC isoforms are fully diverged. Yet, within each isoform a high extent of conservation of respective subdomains is found. This applies to the C- and N-termini, a long linker region between the protein halves (C1b), two short cyclase-transducing-elements (CTE) and notably to the two hexahelical membrane domains TM1 and TM2. Except for the membrane anchor all subdomains were previously implicated in regulatory modalities. The bioinformatic results unequivocally indicate that the membrane anchors must possess an important regulatory function specifically tailored for each mAC isoform.
Purpose
In “Social media’s slippery slope: challenges, opportunities and future research directions”, Schultz and Peltier (2013) asked “whether or how social media can be used to leverage consumer ...engagement into highly profitable relationships for both parties”. The purpose of this article is to continue this discussion by reviewing recent literature on consumer engagement and proposing a framework for future research.
Design/methodology/approach
The paper reviews the marketing literature on social media, paying particular attention to consumer engagement, which was identified as a primary area of concern in Schultz and Peltier (2013).
Findings
A significant amount of research has been conducted on consumer engagement since 2010. Lack of consensus on the definition of the construct has led to fragmentation in the discipline, however. As a result, research related to consumer engagement is often not identified as such, making it difficult for academics and practitioners to stay abreast of developments in this area.
Originality/value
This critical review provides marketing academics and practitioners insights into the antecedents and consequences of consumer engagement and offers a conceptual framework for future research.
Tenosynovial giant cell tumor (TGCT) is a rare benign tumor that involves the synovium, bursa, and tendon sheath, resulting in reduced mobility of the affected joint or limb. The current standard of ...care for TGCT is surgical resection. However, some patients have tumor recurrence, present with unresectable tumors, or have tumors that are in locations where resection could result in amputations or significant debility. Therefore, the development of systemic agents with activity against TGCT to expand treatment options is a highly unmet medical need. Pathologically, TGCT is characterized by the overexpression of colony-stimulating factor 1 (CSF-1), which leads to the recruitment of colony-stimulating factor-1 receptor (CSF-1R) expressing macrophages that make up the primary cell type within these giant cell tumors. The binding of CSF-1 and CSF-1R controls cell survival and proliferation of monocytes and the switch from a monocytic to macrophage phenotype contributing to the growth and inflammation within these tumors. Therefore, molecules that target CSF-1/CSF-1R have emerged as potential systemic agents for the treatment of TGCT. Given the role of macrophages in regulating tumorigenesis, CSF1/CSF1R-targeting agents have emerged as attractive therapeutic targets for solid tumors. Pexidartinib is an orally bioavailable and potent inhibitor of CSF-1R which is one of the most clinically used agents. In this review, we discuss the biology of TGCT and review the pre-clinical and clinical development of pexidartinib which ultimately led to the FDA approval of this agent for the treatment of TGCT as well as ongoing clinical studies utilizing pexidartinib in the setting of cancer.
We evaluated real-time myoelectric pattern recognition control of a virtual arm by transradial amputees. Five unilateral patients performed 10 wrist and hand movements using their amputated and ...intact arms. In order to demonstrate the value of information from intrinsic hand muscles, this data was included in EMG recordings from the intact arm. With both arms, motions were selected in approximately 0.2 s on average, and completed in less than 1.25 s. Approximately 99% of wrist movements were completed using either arm; however, the completion rate of hand movements was significantly lower for the amputated arm (53.9% ± 14.2%) than for the intact arm ( 69.4% ± 13.1%). For the amputated arm, average classification accuracy for only 6 movements-including a single hand grasp-was 93.1% ± 4.1%, compared to 84.4% ± 7.2% for all 10 movements. Use of 6 optimally-placed electrodes only reduced this accuracy to 91.5% ± 4.9%. These results suggest that muscles in the residual forearm produce sufficient myoelectric information for real-time wrist control, but not for performing multiple hand grasps. The outcomes of this study could aid the development of a practical multifunctional myoelectric prosthesis for transradial amputees, and suggest that increased EMG information-such as made available through targeted muscle reinnervation-could improve control of these prostheses .
Alkylation of aromatic rings with alkyl halides is an important transformation in organic synthesis, yet an enzymatic equivalent is unknown. Here, we report that cylindrocyclophane biosynthesis in ...Cylindrospermum licheniforme ATCC 29412 involves chlorination of an unactivated carbon center by a novel halogenase, followed by a previously uncharacterized enzymatic dimerization reaction featuring sequential, stereospecific alkylations of resorcinol aromatic rings. Discovery of the enzymatic machinery underlying this unique biosynthetic carbon-carbon bond formation has implications for biocatalysis and metabolic engineering.
Radioprotective 105 kDa (CD180) is an unusual TLR that lacks an intracellular Toll-IL-1R signaling domain and exhibits unconventional homodimerization behavior. Differential expression and functions ...of radioprotective 105 kDa have been associated with immune-mediated pathologies, including infection, chronic inflammation, and autoimmune disorders. Radioprotective 105 kDa activates macrophages and B cells independently of canonical TLR signaling. Current understanding of the functional consequences of radioprotective 105 kDa signaling in B cells, macrophages, and dendritic cells indicates overlapping, but also some apparent opposing, cell-specific roles for radioprotective 105 kDa in shaping cellular functions. This review compares interactions of radioprotective 105 kDa with its coreceptors, CD19, TLR4, and TLR2; integrates recent, novel findings on radioprotective 105 kDa-mediated molecular signaling mechanisms; and summarizes current understanding of its contributions to infectious, inflammatory, and autoimmune disease.
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