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Alternative Modes (alternative + mode)
Selected AbstractsThinking about flagellar oscillationCYTOSKELETON, Issue 8 2009Charles J. Brokaw Abstract Bending of cilia and flagella results from sliding between the microtubular outer doublets, driven by dynein motor enzymes. This review reminds us that many questions remain to be answered before we can understand how dynein-driven sliding causes the oscillatory bending of cilia and flagella. Does oscillation require switching between two distinct, persistent modes of dynein activity? Only one mode, an active forward mode, has been characterized, but an alternative mode, either inactive or reverse, appears to be required. Does switching between modes use information from curvature, sliding direction, or both? Is there a mechanism for reciprocal inhibition? Can a localized capability for oscillatory sliding become self-organized to produce the metachronal phase differences required for bend propagation? Are interactions between adjacent dyneins important for regulation of oscillation and bend propagation? Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source] Influence of stability on the acute toxicity of CdSe/ZnS nanocrystals to Daphnia magnaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2010Heather E. Pace Abstract The acute toxicity of polymer-coated CdSe/ZnS quantum dots (QDs) to Daphnia magna was investigated using 48-h exposure studies. The principal objective was to relate the toxicity of QDs to specific physical and chemical aspects of the QD. As such, two different CdSe core diameters, 2,nm QDs (green-emitting) and 5,nm QDs (red-emitting), and two different surface coatings, polyethylene oxide (PEO) and 11-mercaptoundecanoic acid (MUA) were studied. The QDs were characterized before and after the 48-h exposure using fluorescence, ultrafiltrations (3 kDa), and inductively coupled plasma-atomic emission spectrometry (ICP-AES) metal analysis. In addition, flow field flow fractionation-inductively coupled plasma-mass spectrometry (Fl FFF-ICP-MS) was used as a more extensive characterization technique to determine particle size and composition as well as identify other potential constituents in the QD solutions. The more stable QDs (PEO) were found to be less acutely toxic than the QDs with accelerated dissolution (MUA), suggesting QD stability has significant impact on the nanoparticles' short-term toxicity. The emergence of dissolved Cd2+ in solution indicates that the toxicity of the MUA QDs is likely due to Cd poisoning, and a mass-based dose response occurred as a consequence of this mode of action. Alternatively, the PEO QDs caused acute toxicity without observed particle dissolution (i.e., no detectable metals were solubilized), suggesting an alternative mode of toxic action for these nanoparticles. Results of the present study suggest that using particle number, instead of mass, as a dose metric for the PEO QDs, produces markedly different conclusions, in that smaller core size does not equate to greater toxicity. Environ. Toxicol. Chem. 2010;29:1338,1344. © 2010 SETAC [source] Early clinical experience with adalimumab in treatment of inflammatory bowel disease with infliximab-treated and naïve patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009A. SWAMINATH Summary Background, Adalimumab, at an induction dose of 160/80 mg followed by 40 mg every other week is approved for treatment of refractory Crohn's disease (CD) and for patients with loss of response to infliximab. Aim, To evaluate the indications for adalimumab, the proportion of inflammatory bowel disease patients who require dose escalation and to identify whether this strategy is effective in inducing or maintaining remission. Methods, Patients prescribed adalimumab for CD were identified and included for analysis, if they had follow-up of at least 6 weeks. Adalimumab dose was escalated if patients had return of symptoms prior to next dose. Clinical judgment was used to determine severity of disease. A second GI physician confirmed disease severity as determined by the first physician. Results, A total of 48 out of 60 patients met inclusion criteria. Adalimumab was used to treat CD in 47/48 (98%) and ulcerative colitis in one (2%). Most patients had moderate 30/48 (63%) or severe 17/48 (35%) disease. Prior infliximab exposure was present in 42/48 (88%). Adalimumab dose escalation occurred in 14/48 (29%) within an average time of 2.2 months (s.d. 1.5 months). A majority of patients who required dose escalation, nine of 14 (64%) did not improve clinically. Steroids could be discontinued in three of 16 (18.8%). Clinical improvement was noted in 21/48 (43.8%) and one of 48 (2%) patients achieved clinical remission. Adverse drug reactions necessitated drug discontinuation in four of 48 (8%) of patients. Conclusions, This retrospective review from a single academic medical centre suggests that a minority of patients, who cannot be maintained on 40 mg every other week, of adalimumab benefit from an increased dose. This suggests the need for a treatment with an alternative mode of action in anti-TNF failures. [source] Vajra Brother, Vajra Sister: Renunciation, Individualism and the Household in Tibetan Buddhist MonasticismTHE JOURNAL OF THE ROYAL ANTHROPOLOGICAL INSTITUTE, Issue 1 2000Martin A. Mills This article challenges two connected notions in the study of Tibetan Buddhism: that Buddhist monasticism is characterized by a pronounced move towards individualism, systematically detaching monks from relational social life; and that Tibetan Buddhist doctrines of karma represent an alternative mode of identity to those constructed within household life. By comparing the ritual practices and inheritance patterns associated with household groups in Ladakh with tantric ritual forms in local Buddhist (Gelukpa) monasteries, it is argued that they demonstrate pronounced structural similarities, centred on the shared symbolic construct of the household/temple as the source of socialized agency. An analysis of the meditative disciplines of Gelukpa monasticism is used to show how such training serves not to renounce kinship and household values, but to transform them into modes of religious authority, essential to the social position of monks (trapa) and incarnate lamas (tulku) in Tibetan Buddhism. [source] DigitAlia , The Other Digital PracticeARCHITECTURAL DESIGN, Issue 2 2010Marjan Colletti Abstract Marjan Colletti, the guest-editor of this issue, defines a clear political agenda for DigitAlia as an alternative mode of digital practice. He outlines how it potentially absorbs the latest digital techniques while embracing the poetic and knowledge of cultural traditions and pushing the very boundaries of creativity. The scope of Colletti's ideas is illustrated by images from his own practice with Marcos Cruz, marcosandmarjan architects, and those of his students at the Bartlett School of Architecture (UCL), the University of Westminster in London and Innsbruck University in Austria. Copyright © 2010 John Wiley & Sons, Ltd. [source] Tumor necrosis factor,neutralizing therapies improve altered hormone axes: An alternative mode of antiinflammatory actionARTHRITIS & RHEUMATISM, Issue 7 2006Rainer H. Straub First page of article [source] Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of actionBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004B. Pollock Summary Background, ,Acne affects 83,95% of 16-year-olds of both sexes, and many seek help from a clinician. Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne. Objectives, To study the efficacy of aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of acne and to identify the mode of action, looking specifically at the effects on surface numbers of P. acnes and on sebum excretion. Methods, ,Ten patients (nine men and one woman, age range 16,40 years) with mild to moderate acne on their backs were recruited. Each patient's back was marked with four 30-cm2 areas of equal acne severity. Each site was then randomly allocated to either ALA-PDT treatment, light alone, ALA alone or an untreated control site. At baseline, numbers of inflammatory and noninflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX, U.S.A.) and surface P. acnes swabs performed. ALA cream (20% in Unguentum Merck) was applied under occlusion to the ALA-PDT and ALA alone sites for 3 h. Red light from a diode laser was then delivered to the ALA-PDT and light alone sites (635 nm, 25 mW cm,2, 15 J cm,2). Each patient was treated weekly for 3 weeks. At each visit acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P. acnes swabs were repeated. Results, There was a statistically significant reduction in inflammatory acne lesion counts from baseline after the second treatment at the ALA-PDT site but not at any of the other sites. No statistically significant reduction in P. acnes numbers or sebum excretion was demonstrated at any sites including the ALA-PDT site. Conclusions, ALA-PDT is capable of clinically improving acne. An alternative mode of action for ALA-PDT other than direct damage to sebaceous glands or photodynamic killing of P. acnes is suggested from the results of this study. [source] Evidence for the effectiveness of sterile injecting equipment provision in preventing hepatitis C and human immunodeficiency virus transmission among injecting drug users: a review of reviewsADDICTION, Issue 5 2010Norah Palmateer ABSTRACT Aims To review the evidence on the effectiveness of harm reduction interventions involving the provision of sterile injecting equipment in the prevention of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). The interventions assessed were needle and syringe programmes (NSP), alternative modes of needle/syringe provision (pharmacies, vending machines and outreach) and the provision of injecting equipment other than needles/syringes. Methods Systematic searches of the English language literature to March 2007 were undertaken to identify systematic, narrative or meta-analytical reviews (also known as a review of reviews) of the impact of interventions on HCV transmission, HIV transmission or injecting risk behaviour (IRB). Critical appraisal criteria classified the reviews as either high quality (,core') or supplementary: a framework based on the quality of reviews, the reviewers' conclusions and the designs/findings of the primary studies was used to derive evidence statements. Results Three core and two supplementary reviews of injecting equipment interventions were identified. According to the proposed framework, this study found (a) insufficient evidence to conclude that any of the interventions are effective in preventing HCV transmission; (b) tentative evidence to support the effectiveness of NSP in preventing HIV transmission; (c) sufficient evidence to support the effectiveness of NSP (and tentative evidence of an additional impact of pharmacy NSP) in reducing self-reported IRB; and (d) little to no evidence on vending machines, outreach or providing other injecting equipment in relation to any of the outcomes. Conclusions The evidence is weaker than given credit for in the literature. The lack of evidence for effectiveness of NSP vis-à-vis biological outcomes (HCV and HIV incidence/prevalence) reflects the limitations of studies that have been undertaken to investigate these associations. Particularly for HCV, low levels of IRB may be insufficient to reduce high levels of transmission. New studies are required to identify the intervention coverage necessary to achieve sustained changes in blood-borne virus transmission. [source] Shifting voices, oppositional discourse, and new visions for communication studiesJOURNAL OF COMMUNICATION, Issue 1 2001L L Putnam This address, delivered at ICA's 50th anniversary conference, calls on the association to take stock of where we are and how we should come together. It reviews 3 periods in the field's recent past: fermentation, fragmentation, and legitimation. Then, drawing from several of Bahktin's notions of dialogue, it summons scholars to come together by engaging in alternative modes of discourse - ones that center on multiple and shifting voices and oppositional discourse. It advocates using the construct of voice rather than paradigms, theories, and academic divisions, to develop complementary ways of understanding. In particular, it calls on the field to take inventory of multiple and shifting voices in reviews and critiques of the literature, to connect with each other through exploring shifting concepts and theories, and to engage in joint actions in ways that embrace and preserve differences. [source] Alternate delivery route for amifostine as a radio-/chemo-protecting agentJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2008Natalie P. Praetorius Amifostine (ethiofos, WR-2721) is an organic thiophosphate prodrug that serves as an antineoplastic adjunct and cytoprotective agent useful in cancer chemotherapy and radiotherapy. The selective protection of certain tissues of the body is believed to be due to higher alkaline phosphatase activity, higher pH and vascular permeation of normal tissues. Amifostine is conventionally administered intravenously before chemotherapy or radiotherapy. It is approved by the Food and Drug Administration (FDA) to reduce cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. It was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer although this indication was withdrawn in 2005. Amifostine is also FDA approved for patients with head and neck cancer to reduce the incidence of moderate to severe xerostomia in patients who are undergoing postoperative radiation treatment where the radiation port includes a substantial portion of the parotid glands. The potential of amifostine as a cytoprotective agent is unlikely to be fully realized if the method of administration is restricted to intravenous administration. Attempts have been made to develop non-invasive methods of delivery such as transdermal patches, pulmonary inhalers, and oral sustained-release microspheres. It is the goal of this article to explore non-intravenous routes of administration associated with better efficacy of the drug. This review will primarily focus on the variety of more recently studied (2002 and later) alternative modes for amifostine administration, including subcutaneous, intrarectal and oral routes. [source] Writing the West: Critical Approaches to ShaneLITERATURE COMPASS (ELECTRONIC), Issue 1 2007Ruth Griffin Representations of the American West have perhaps resonated most strongly in the western film genre, yet at the same time, the literary western is a highly developed and sophisticated genre in its own right. Meanwhile, critical approaches to the West have become increasingly wide-ranging, spanning historical/literary studies; film/cultural studies; genre; gender studies; philosophy, structuralism and, most recently, post-modernism. In light of such critical diversity, this article places a literary text alongside a western film in order to illustrate and demonstrate potential critical approaches to the western. To this end it takes Jack Schaefer's novel Shane as its case study with two main organising principles in mind. Firstly, analysis of the text demonstrates the ways in which critical methods and theoretical debates can be applied to the literary western. As a result, I assess, for example, the convention which applies historical co-ordinates to fictional representations, as well as the challenges posed by alternative modes of critique. Secondly, the novel is placed alongside the filmic adaptation in order to demonstrate the fluid nature of western forms and the critical approaches which can be used to analyse them. Finally, I offer my own perspective, suggesting that the methodologies and textual forms explored in the article signal the need for trans-disciplinary critical approaches which reflect both the simplicity and the diversity of the western as a whole. [source] Cell,cell communication in filamentous cyanobacteriaMOLECULAR MICROBIOLOGY, Issue 4 2008Robert Haselkorn Summary Although cytoplasmic bridges between adjacent cells in the filaments of nitrogen-fixing cyanobacteria have been known for decades, the existence also of a continuous periplasm along the filaments raised the possibility that alternative modes of communication between cells could be utilized. The latter hypothesis was investigated by using GFP fusions to proteins whose expression is cell-specific and engineered to be transported into the periplasm. Two groups have recently obtained contradictory results, one supporting periplasmic transport of GFP from cell to cell, the other not. A third effort, involving members of the first group, used a smaller, soluble fluorophore and found rapid communication via the cytoplasmic bridges between cells. The dilemma of periplasmic diffusion remains unresolved. [source] Pathogen-induced resistance and alarm signals in the phloemMOLECULAR PLANT PATHOLOGY, Issue 5 2004AART J. E. VAN BEL SUMMARY Despite a long-standing notion of long-distance signals triggering systemic acquired resistance (SAR), the translocation pathway and the identity of the signals involved have not been determined with any degree of certainty. A critical assessment indicates that, in parallel to signalling via the phloem, alternative modes for SAR induction such as signalling via the xylem or air-borne signalling by volatile substances may occur. This review further evaluates several classes of compounds as being functional in systemic resistance signalling. Evidence in favour of SAR involvement of phloem-mobile substances such as salicylic acid, lipid-derived molecules, reactive oxygen species and components of the antioxidant machinery is contradictory, circumstantial or inconclusive, at best. Nitric oxide bound to proteins or thiols seems a good candidate for signalling, but has not been found in phloem sap thus far. No convincing support of the involvement in SAR of phloem-mobile substances such as calcium, oligosaccharides, peptides or RNA species, which function in other systemic signalling cascades, has yet been produced. Nevertheless, phloem-mobile macromolecules are considered as potential tools for SAR given their pivotal role in remote gene expression under stress conditions. In this framework, the existence of several cascades for signal generation along the phloem pathway is envisaged. Finally, recent methods for detection of molecular signals in phloem sap and their expression in companion cells are presented. [source] LOFAR as a probe of the sources of cosmological reionizationMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY: LETTERS (ELECTRONIC), Issue 1 2005Saleem Zaroubi ABSTRACT We propose use of the thickness of the ionization front as a discriminant between alternative modes of reionization in the early Universe, by stars or by miniquasars. Assuming a photoionization,recombination balance, we find that for miniquasar sources the transition from neutral to ionized intergalactic medium is extended and has two features. The first is a sudden steep increase in the neutral fraction with a typical width of 5,10 comoving megaparsecs, depending on the miniquasar power. The second feature is a long wing that represents a much slower transition from a neutral fraction of , 0.8 to 1. The angular resolution of LOFAR is expected to resolve these scales and will, therefore, play an important role in discriminating the hard sources of ionizing photons from the stellar ones. [source] Two alternative modes for optimizing nylon-6 byproduct hydrolytic activity from a carboxylesterase with a ,-lactamase fold: X-ray crystallographic analysis of directly evolved 6-aminohexanoate-dimer hydrolasePROTEIN SCIENCE, Issue 8 2009Taku Ohki Abstract Promiscuous 6-aminohexanoate-linear dimer (Ald)-hydrolytic activity originally obtained in a carboxylesterase with a ,-lactamase fold was enhanced about 80-fold by directed evolution using error-prone PCR and DNA shuffling. Kinetic studies of the mutant enzyme (Hyb-S4M94) demonstrated that the enzyme had acquired an increased affinity (Km = 15 mM) and turnover (kcat = 3.1 s,1) for Ald, and that a catalytic center suitable for nylon-6 byproduct hydrolysis had been generated. Construction of various mutant enzymes revealed that the enhanced activity in the newly evolved enzyme is due to the substitutions R187S/F264C/D370Y. Crystal structures of Hyb-S4M94 with bound substrate suggested that catalytic function for Ald was improved by hydrogen-bonding/hydrophobic interactions between the AldCOOH and Tyr370, a hydrogen-bonding network from Ser187 to AldNH, and interaction between AldNH and Gln27-O, derived from another subunit in the homo-dimeric structure. In wild-type Ald-hydrolase (NylB), Ald-hydrolytic activity is thought to be optimized by the substitutions G181D/H266N, which improve an electrostatic interaction with AldNH (Kawashima et al., FEBS J 2009; 276:2547,2556). We propose here that there exist at least two alternative modes for optimizing the Ald-hydrolytic activity of a carboxylesterase with a ,-lactamase fold. [source] PUBLIC SECTOR REFORM IN DUTCH HIGHER EDUCATION: THE ORGANIZATIONAL TRANSFORMATION OF THE UNIVERSITYPUBLIC ADMINISTRATION, Issue 1 2007HARRY F DE BOER During the past few decades traditional state-centred governing arrangements have been critiqued and replaced by alternative modes of governance. Higher education is one of the public sectors where such shifts in governance have been seen. As a consequence of the reshuffling of authority and responsibilities across the different levels in Dutch higher education, universities as organizations have become important foci of attention in the system's coordination. The main question addressed in this article is to what extent we can speak of an organizational transformation of Dutch universities. Based on conceptual ideas from researchers such as Greenwood and Hinings (1996), Ferlie et al. (1996), and Brunsson and Sahlin-Andersson (2000), we use a framework that focuses attention on the concepts of the construction of identity, hierarchy and rationality to systematically analyse the various aspects of transformations of professional organizations. [source] The nature of publishing and assessment in Geography and Environmental Studies: evidence from the Research Assessment Exercise 2008AREA, Issue 3 2009Keith Richards We present a summary of the kinds of outputs submitted to the Geography and Environmental Studies sub-panel (H-32) for the 2008 Research Assessment Exercise (RAE), and examine the relationships between the peer assessment of research quality that the RAE process has typified, and alternative modes of assessment based on bibliometrics. This comparison is effected using (in aggregate form) some of the results from the RAE, together with citation data gathered after completion of the RAE assessment, specifically for the purpose of this paper. We conclude that, if it continues to be necessary and desirable to assess, in some measure and however imprecisely, research quality, then peer assessment cannot be replaced by bibliometrics. Bibliometrics permit measurement of something that may be linked to quality but is essentially a different phenomenon , a measure of ,impact', for example. [source] | ||||||||||||||||